The long term objective of this research proposal is to determine the role of the primary cilium in podocytes. In the progression of proteinuric renal diseases, there are alterations in podocyte appearance, e.g. pseudocysts and foot process effacement. Renal collecting duct cells have now been shown to sense fluid flow by the apical plasma membrane's primary cilium in vitro. Since podocytes are anatomically located in an area of high fluid flow, one hypothesis would be that the podocyte's primary cilium senses fluid flow. This major hypothesis is integrated into four specific aims. The first aim will employ standard imaging techniques to determine the podocyte cilia in terms of length, frequency, and microtubular arrangement. The second aim will address the hypothesis that podocytes can sense fluid flow by monitoring changes in intracellular Ca++. Intracellular calcium will be monitored using a standard perfusion apparatus and microscope. The third aim will use biophysical and biochemical manipulation of the primary cilium to determine if the primary cilium is a flow sensing organelle. The fourth aim will identify which intracellular and extracellular calcium channels are involved, e.g. polycystins and transient receptor potential channels (TRPC), in the flow induced response. Ca++.